Papel da heme-oxigenase na ação da peçonha de Bothrops jararacussu / Role of heme oxygenase in the action of Bothrops jararacussusnake venom

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Heme-oxygenase (HO) is an enzyme involved in the degradation of heme groups that results in the formation of biliverdin IX, iron and carbon monoxide. At low concentrations, these reaction products have anti-apoptotic, anti-inflammatory, anti-proliferative, and anti-thrombotic activities, whereas at high concentrations they can cause hypoxia, neurological damage, mitochondrial dysfunction and hiperbilirrubinemia. In this study, we investigated the involvement of HO in the increase in vascular permeability, hemorrhage and myonecrosis caused by Bothrops jararacussu snake venom. Bothrops jararacussu venom (0.3-3 µg/site) increased the vascular permeability in mouse dorsal skin. This increase was inhibited by zinc deuteroporphyrin 2,4-bis-glycol (ZnDPBG), a non-selective HO inhibitor, when administered i.p. (45 and 90 µmol/kg). In contrast, ZnDPBG given i.d. (25-200 µmol/site) did not affect the increase in vascular permeability. Co-treatment with the nitric oxide synthase inhibitor N?-nitro-L-arginine methyl ester (L-NAME, 100 nmol/site) did not potentiate the inhibition by ZnDPBG. ZnDPBG (45 or 90 µmol/kg, i.p.) did not reduce the dorsal skin hemorrhage (3 and 10 µg of venom/site), but rather, increased this response at the highest dose. Venom (25 and 75µg) increased the HO activity of mouse gastrocnemius muscle. The increase in activity was biphasic and included early (first few hours after envenoming, corresponding to acute damage) and late (7-18 days after envenoming - muscle regeneration) phases. Enhanced gene expression of HO-1 was seen 3-12 h after envenomation (75 µg), with little change in HO-2 expression. Histological analysis showed that the muscle damage consisted of three phases: phase 1 (up to 6-12 h post-venom), characterized mostly by hemorrhage and myonecrosis, phase 2 (12-72 h post-venom), characterized by an extensive inflammatory infiltrate, and phase 3 (7-28 days post-venom), characterized mainly by regenerative cells and an increase in collagen deposition around these cells. Treatment with ZnDPBG (90 µmol/kg, i.p.) 15 min after venom (75 µg) injection partially attenuated the myonecrosis and also decreased the creatine kinase (CK) levels after 1 and 3 h. Together, these results indicate that HO activity is involved in the edema and myonecrosis caused by B. jararacussu venom, and that the inhibition of this activity with ZnDPBG provides some protection against these local effects.

ASSUNTO(S)

heme oxygenase (decyclizing) hemorrhage bothrops myonecrosis hemorragia mionecrose monoxido de carbono carbon monoxide permeabilidade vascular vascular permeability heme oxigenase (desciclizante)

ACESSO AO ARTIGO

Documentos Relacionados